Abstract
Background
Type III collagen of the interstitial matrix is highly expressed in fibrotic tissue of Crohn’s disease (CD) and suggested to undergo remodelling during the characteristic deep tissue inflammation. Periods of inflammatory flares and remission could thus be reflected by varying degrees of type III collagen degradation and formation in relation to fibrogenesis and resolution of fibrosis. The aim was to investigate the association between type III collagen remodelling and CD disease phenotypes based on the Montreal classification
Methods
40 CD patients were endoscopically assessed according to the Montreal B classification (luminal or stricturing phenotype) and Harvey Bradshaw Index for clinical disease activity (<4 = inactive; >4 = active). Patients were stratified based on both the Montreal B classification and HBI scores. Biomarkers were assessed by ELISA: 1) CTX-III (cross-linked protease degraded fragments of type III collagen), PC3X (cross-linked type III collagen formation), 3) PRO-C3 (type III collagen formation), and 4) C3M (MMP-9 degradation fragments)
Results
Biomarker levels of CTX-III was significantly elevated in CD patients with luminal- and clinically inactive- disease compared to patients with stricturing- and clinically inactive- disease and luminal- and clinically active- disease (p<0.01 and p<0.05, fig 1A). The levels of net fibrolysis of cross-linked type III collagen (CTX-III/PC3X) was significantly higher in patients with luminal- and clinically inactive- disease compared to patients with stricturing- and clinically inactive- disease (p<0.001), luminal- and clinically active- disease (p<0.001), and patients with stricturing- and clinically active- disease (p<0.05, fig 1C). Significantly elevated levels of net type III collagen degradation (C3M/PRO-C3) were observed in patients with a luminal- and clinically active- disease compared to luminal- and clinically inactive- as well as stricturing- and clinically inactive- disease (p<0.05). Furthermore, net type III collagen degradation was elevated compared to patients with stricturing- and clinically active- disease (p<0.05, fig 1F). Biomarker levels of PC3X, C3M, and PRO-C3 were unable to differentiate between patient groupings (fig 1B, D, and E)
Conclusion
Proteolytic degradation of cross-linked type III collagen (CTX-III) reflecting resolution of fibrosis in CD patients with luminal disease, may be associated with a protective effect against fibrogenesis and progression to fibrostenosis. These data indicate differences in cross-linked and non-cross-linked type III collagen remodelling in CD patients, and their potential use for differentiating patient phenotypes and disease activity
TGF-β Induced Collagen Remodelling by IPF Fibroblasts is Alleviated by Inhibition of Lysyl Oxidase Enzyme Activity